PMID- 7929438
OWN - NLM
STAT- MEDLINE
DCOM- 19941123
LR  - 20220311
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 43
DP  - 1994 Oct 28
TI  - Multiple sites of the propeptide region of human stromelysin-1 are required for 
      maintaining a latent form of the enzyme.
PG  - 26982-7
AB  - Latency of matrix metalloproteinase 3 (MMP-3) is regulated by the interaction of 
      a free cysteine residue (Cys-75) in the conserved amino acid sequence 
      Pro-Arg-Cys-Gly-Val-Pro-Asp located in the COOH-terminal portion of the 
      propeptide with a chelated zinc atom in the active site of the catalytic domain. 
      Proteolytic activation of full-length human pro-MMP-3 involves the removal of 
      approximately 35 amino acids from the NH2-terminal portion of the propeptide, 
      forming a 53-kDa unstable intermediate that undergoes intermolecular 
      autocatalysis to form the 45-kDa mature active enzyme. In this study, we have 
      evaluated the contribution of the NH2-terminal 35 amino acids to the maintenance 
      of latency. Full-length human pro-MMP-3 was expressed in Escherichia coli and 
      refolded to form latent pro-MMP-3 capable of activation by chymotrypsin or 
      aminophenylmercuric acetate. Renaturation of pro-MMP-3 expressed in bacteria with 
      20 or more amino acids removed from the NH2-terminal region of the propeptide 
      yielded only an active enzyme. COS-7 cells transiently transfected with pro-MMP-3 
      expression vectors containing the single amino acid substitutions Y20A, L21A, and 
      C75S also secreted active forms of the enzyme. These data suggest that 
      simultaneous interactions of the NH2- and COOH-terminal regions of the propeptide 
      are required for maintenance of the latent form of the enzyme.
FAU - Freimark, B D
AU  - Freimark BD
AD  - Department of Inflammatory Disease Research, DuPont Merck Pharmaceutical Company, 
      Wilmington, Delaware 19880-0400.
FAU - Feeser, W S
AU  - Feeser WS
FAU - Rosenfeld, S A
AU  - Rosenfeld SA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Enzyme Precursors)
RN  - 0 (Protein Sorting Signals)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cells, Cultured
MH  - DNA Mutational Analysis
MH  - Enzyme Activation
MH  - Enzyme Precursors/genetics/*metabolism
MH  - Enzyme Stability
MH  - Escherichia coli/genetics
MH  - Humans
MH  - Matrix Metalloproteinase 3
MH  - Metalloendopeptidases/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Protein Folding
MH  - Protein Processing, Post-Translational
MH  - Protein Sorting Signals/genetics/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Sequence Deletion
MH  - Structure-Activity Relationship
EDAT- 1994/10/28 00:00
MHDA- 1994/10/28 00:01
CRDT- 1994/10/28 00:00
PHST- 1994/10/28 00:00 [pubmed]
PHST- 1994/10/28 00:01 [medline]
PHST- 1994/10/28 00:00 [entrez]
AID - S0021-9258(18)47115-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Oct 28;269(43):26982-7.